Hi Seham,

Designing primers for ChIP-QPCR is generally similar to designing normal QPCR primers in terms of steps, many online primer designing tools could do the work, such as primer3 or NCBI primer blast etc. However, there are some tips need to be careful when designing ChIP primers.

• Low Tm temperature is not uncommon. The transcription factor(TF) binding sites are usually located in promoters, UTR, or even intron regions of the genes of interest. These regions may be high with A/T sequence, making the primer pair with low Tm. However as long as the primers are specific, use relatively higher annealing temperature (5°C below Tm is not necessary) should be fine. Don't be too disappointed if the primers score is lower than your expect :)
• Checking cis-regulatory elements may be helpful. Because of the low quantity of the ChIP DNA, sometimes we have to focus on the ROI rather than testing primers that cover all of the promoter regions. Design primers that cover or near the cis-regulatory elements such as conserved non-coding sequences, reported TF binding sites may be helpful.
• Test primer specificity and efficiency using genome DNA. The primer specificity and primer efficiency are critical for ChIP-QPCR data analysis, always test them using genome DNA before you performing QPCR with the ChIP DNA sample.

Good luck with your ChIP-QPCR :D

Some more things to think about:

Amplicon size- What size are your fragments relative to your amplicon? If your primers are making a 200bp amplicon, and you have sonicated so that your DNA is in 300bp fragments +/- 200bp, it will be less likely that both primers will find their targets on one fragment of ChIP DNA than if your amplicon size was around 75-100bp. So I prefer less than 150bp amplicon size when I have the option.

Where do you think your protein of interest will bind DNA?- Some ChIP target proteins have known binding sequences, others do not. If you are in the category where you don't know where your protein will bind, a good place to start is in the neighborhood of transcription start sites (TSSs) of genes that are impacted in your system. Otherwise, another way is to look where other things bind near genes of interest. Find ChIP-seq data sets and see if several other proteins are known to bind to a particular area near a TSS of a gene of interest, as proteins on DNA usually form a large complex at a given site, and your protein could be there as well. 

I have used primer blast to generate possible primers and then used in-silico PCR to confirm they are where and what I want. Using UCSC in-silico PCR you can visualize where your amplicon is in relation to your gene of interest and ChIP-seq read density tracks, which I have found helpful.

Ultimately though, ChIP-PCR primers can be trial and error, so order several for each gene you want to analyze to increase your chances of hitting a place where you can measure a significant change in enrichment of your protein of interest.

I hope this helps. Best of luck!

 Thank you very much Rui Mo  and Robert Jackson Mobley